Bone marrow suppressing agents

Abstract

The invention concerns a method for suppressing bone marrow which comprises administering to a mammal at least one bone marrow suppressing complex of a radionuclide selected from the group consisting of Samarium-153, Gadolinium-159, and Holmium-166 and 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid a physiologically acceptable salt thereof. Suitable compositions for use in this method are also provided.

We claim: 
     
       1. A method for suppressing bone marrow which comprises administering to a mammal in need of such treatment a bone marrow suppressing amount of at least one bone marrow suppressing composition comprising at least one radionuclide selected from the group consisting of Samarium-153, Gadolinium-159, and Holmium-166 complexed with 1,4,7, 10-tetraazacyclododecanetetramethylenephosphonic acid or a physiologically acceptable salt thereof. 
     
     
       2. The method of claim 1 wherein the radionuclide is Samarium-153. 
     
     
       3. The method of claim 1 wherein the radionuclide is Gadolinium-159. 
     
     
       4. The method of claim 1 wherein the radionuclide is Holmium-166. 
     
     
       5. The method of claim 1 used in conjunction with an additional treatment regimen using at least one of (a) one or more bone marrow suppressing agents, and/or (b) one or more chemotherapeutic agents, and/or (c) one or more radiotherapeutic agents or radiotherapeutic methods. 
     
     
       6. The method of claim 1 used in conjunction with total body irradiation or targeted external irradiation. 
     
     
       7. The method of claim 1 including the additional step of bone marrow transplantation after sufficient bone marrow suppression is achieved. 
     
     
       8. The method of claim 1 used in conjunction with one or more therapeutic regimens for the treatment of leukemia, lymphoma, myeloma or Hodgkin's disease. 
     
     
       9. The method of claim 8 wherein the disease being treated is a leukemia. 
     
     
       10. The method of claim 8 wherein the disease being treated is a lymphoma. 
     
     
       11. The method of claim 8 wherein the disease being treated is a myeloma. 
     
     
       12. The method of claim 8 wherein the disease being treated is Hodgkin's disease. 
     
     
       13. The method of claim 1 used in conjunction with a treatment employing at least one chemotherapeutic agent. 
     
     
       14. The method of claim 13 wherein the chemotherapeutic agent is selected from dimethyl busulfan, cyclophosphamide, bischloroethyl nitrosourea, cytosine arabinoside, and 6-thioguanine. 
     
     
       15. The method of claim 1 used in conjunction with total body irradiation and with a treatment employing at least one chemotherapeutic agent. 
     
     
       16. The method of claim 15 wherein the chemotherapeutic agent is selected from dimethyl busulfan, cyclophosphamide, bischloroethyl nitrosourea, cytosine arabinoside, and 6-thioguanine. 
     
     
       17. A sterile composition suitable for administration to a mammal suppressing bone marrow comprising at least one radionuclide selected from the group consisting of Samarium-153, Gadolinium-159, and Holmium-166 complexed with 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid or a physiologically-acceptable salt thereof and wherein the radionuclide in dosage form is present in an amount containing from about 18 to about 1850 megabecquerels per kilogram of body weight of said mammal. 
     
     
       18. The composition of claim 17 wherein the ligand to radionuclide ratio is from 1:1 to 2:1. 
     
     
       19. The composition of claim 17 wherein the dosage form contains from about 185 to about 1850 mega-becquerels per kilogram of body weight of said mammal. 
     
     
       20. The composition of claim 19 wherein the macrocyclic ligand is 1,4,7,10-tetraazacyclododecanetetramethylenephosphonic acid. 
     
     
       21. The composition of claim 20 wherein the radionuclide is Sm-153. 
     
     
       22. The composition of claim 20 wherein the radionuclide is Ho-166. 
     
     
       23. The composition of claim 20 wherein the radionuclide is Gd-159. 
     
     
       24. The composition of claim 17 wherein the radionuclide is Sm-153. 
     
     
       25. The composition of claim 17 wherein the radionuclide is Ho-166. 
     
     
       26. The composition of claim 17 wherein the radionuclide is Gd-159. 
     
     
       27. A pharmaceutical formulation comprising the composition of claim 17 in a pharmaceutically acceptable carrier. 
     
     
       28. The composition of claim 27 wherein the radionuclide is Sm-153. 
     
     
       29. The composition of claim 27 wherein the radionuclide is Ho-166. 
     
     
       30. The composition of claim 27 wherein the radionuclide is Gd-159.